Functional rescue of beta-adrenoceptor dimerization and trafficking by pharmacological chaperones.

ABSTRACT: Site-directed mutagenesis guided by evolutionary trace analysis revealed that substitution of V179 and W183 within a cluster of evolutionarily important residues on the surface of the fourth transmembrane domain of the beta(1)-adrenergic receptor (beta(1)AR) significantly reduced the propensity of the receptor to self-assemble into homodimers as assessed by bioluminescence resonance energy transfer in living cells. These results suggest that mutation of V179 and W183 result in conformational changes that reduce homodimerization either directly by interfering with the dimerization interface or indirectly by causing local misfolding that result in reduced self-assembly. However, the mutations did not cause a general misfolding of the beta(1)AR as they did not prevent heterodimerization with

SUBMITTER: Kobayashi H 

PROVIDER: S-EPMC2755524 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature